Copenhagen researchers identify brain cell target for schizophrenia cognitive symptoms

For people living with schizophrenia, the cognitive weight can be as disabling as the hallucinations and delusions that define the illness in popular understanding. Forgetting what you started to do. Struggling to concentrate on a conversation. Finding ordinary tasks—paying a bill, following a recipe, holding down a job—exhausting or impossible. These cognitive symptoms have no adequate treatment. Current medications don't touch them. That gap is what drew researchers at the University of Copenhagen to a question: what if you could intervene before the brain's compensatory systems finally fail?

Schizophrenia emerges from abnormal brain development, sometimes beginning before birth. But the illness typically stays silent for years. The brain, it seems, has a remarkable capacity to work around early damage—until suddenly it doesn't. Katarina Dragicevic, one of the study's lead authors, traced this arc by tracking brain development from the fetal stage into adulthood in mice. What she found was a critical threshold. Until the transition from childhood to adolescence, the molecular and functional changes in the brain remained relatively minor, which may explain why symptoms don't appear until later. But late in development, everything shifts dramatically. "Our study shows that until a specific point, brain development is largely unaffected by changes," Dragicevic said. "The period leading up to that point may represent a treatment window where we can prevent functional impairment."

To identify what goes wrong at that turning point, the researchers worked with mice carrying a genetic mutation called 15q13.3 microdeletion syndrome—a condition linked in humans to epilepsy, schizophrenia, autism, and other neurodevelopmental disorders. They used sleep as their window into brain function. Sleep disruption is common in psychiatric illness, and it's observable, measurable. By examining both the animals' sleep behavior and the activity of specific brain cell types, they discovered something striking: one particular type of brain cell was significantly overactive in the affected mice compared to healthy controls.

These cells are easy to miss. They represent only a tiny fraction of the brain's total population. Yet they wield outsized influence over brain function. When the researchers used a technique called chemogenetics to suppress the activity of these cells, the mice's sleep patterns normalized. More than that—the reduction in cell activity appeared to alleviate other psychiatric symptoms as well. "This means that this type of brain cell plays a critical role in sleep in mice with this syndrome," said Navneet A. Vasistha, an assistant professor at the Biotech Research and Innovation Center and one of the study's lead authors. "Using chemogenetics, we can reduce the activity of these cells and restore normal sleep patterns—potentially alleviating other psychiatric symptoms as well."

The implications are significant but measured. Researchers are nowhere near testing this approach in humans. Drug development from a mouse study to a clinical trial is a long, uncertain road. But the discovery points toward a different kind of treatment—one that doesn't flood the brain with broad-spectrum drugs that affect millions of cells and produce a cascade of side effects. Instead, it suggests the possibility of a therapy so precisely targeted that it acts on a single cell type, minimizing collateral damage. "This cell type could potentially become a treatment target," Vasistha said. "We hope that in the future, patients will benefit from a therapy for cognitive disorders that doesn't broadly affect brain cells, but is so precisely targeted that side effects can be minimized." The study appears in the journal Neuron. What happens next depends on whether researchers can translate this mouse model into a drug that works in the human brain—and whether that drug can do what the mice's brains learned to do: restore function before the chain snaps.